The aim of my PhD is to elucidate on a cellular level, why proton and photon radiotherapy results in different clinical outcomes and especially, how the DNA double strand break (DSB) repair, subsequent to the respective irradiation, differs. The DNA double strand break repair is mainly accomplished by the fast but erroneous Non-homologous end joining (NHEJ) and additionally, the more laborious, but theoretically error-free, Homologous recombination repair (HRR). Previous data strongly suggests a dependence of proton-induced DSBs on the repair by HRR, which could provide an opportunity for improved patient stratification depending on the genetic background, respectively for combination therapy with HRR-corrupting drugs. Therefore, I combined proton radiotherapy with Ganetespib to inhibit HSP90, a protein that fixes and stabilizes versatile proteins such as HRR key proteins FANCD2, BRCA1, BRCA2, or FANCA and therefore demonstrated a downregulating effect of HRR. [1-3] Recent data, suggests a synergistic effect of Ganetespib and proton irradiation on reduced cancer cell survival. As a next step, we would like to investigate this effect on the direct level of damaged DNA and how the cellular repair can deal with it, upon Ganetespib treatment which can be achieved by alkaline COMET assay.